4-Alkoxy cyclohexane-1 amino carboxylic acid esters and method for the production thereof

ABSTRACT

The invention relates to novel 4-alkoxy-cyclohexane-1-amino-carboxylic esters of the formula (IV)  
                 
 
     in which R 1  represents OR 3 , R 2  represents alkyl, and R 3  represents alkyl, to intermediates and processes for their preparation, and to their use as intermediates in the synthesis of insecticidal, acaricidal, and herbicidal compounds or pharmaceutically active compounds.

[0001] The invention relates to novel4-alkoxy-cyclohexane-1-amino-carboxylic esters, to intermediates andprocesses for their preparation and to their use as intermediates in thesynthesis of insecticidal, acaricidal and herbicidal compounds orpharmaceutically active compounds.

[0002] Substituted cyclic aminocarboxylic acids can generally beobtained by the Bucherer-Bergs synthesis or by the Strecker synthesis,resulting in each case in different isomeric forms. Thus, using theconditions of the Bucherer-Bergs synthesis in the preparation of thesubstituted cyclic aminocarboxylic acids of the general formula (I)

[0003] give predominantly the isomer (I-a),

[0004] in which the radical R¹ and the amino group are arranged cis toone another, whereas the conditions of the Strecker synthesis givepredominantly the trans isomer (I-b)

[0005] (J. Chem. Soc. 1961, 4372-4379; Chem. Pharm. Bull. 21 (1973)685-691; Chem. Pharm. Bull. 21 (1973) 2460-2465; Can. J .Chem. 53 (1975)3339-3350).

[0006] The Bucherer-Bergs reaction is generally carried out by reactinga substituted cyclic ketone of the general formula (II)

[0007] in a solvent or solvent mixture with ammonium carbonate and analkali metal cyanide, generally sodium cyanide or potassium cyanide,followed by isolation of the resulting hydantoin of the general formula(III)

[0008] Here, the hydantoins of the general formula (III) are usuallyobtained as mixtures of the cis isomers (III-a)

[0009] and trans isomers (III-b)

[0010] The hydantoins of the general formula (III) are subsequentlyhydrolysed by known methods, under acidic or alkaline conditions, togive the substituted cyclic aminocarboxylic acids of the general formula(I).

[0011] The substituted cyclic aminocarboxylic acids of the generalformula (I) can then be esterified by known methods of organic chemistryto give the substituted cyclic aminocarboxylic esters of the generalformula (IV)

[0012] We have found novel compounds of the formulae (IV-a) and (IV-b)

[0013] in which

[0014] R¹ represents OR³,

[0015] R² represents alkyl and

[0016] R³ represents alkyl.

[0017] Preference is given to compounds of the formulae (IV-a) and(IV-b), in which

[0018] R¹ represents OR³,

[0019] R² represents C₁-C₆-alkyl and

[0020] R³ represents C₁-C₄-alkyl.

[0021] Particular preference is given to compounds of the formulae(IV-a) and (IV-b) in which

[0022] R¹ represents OR³,

[0023] R² represents methyl, ethyl, n-propyl or n-butyl and

[0024] R³ represents methyl, ethyl, n-propyl, n-butyl or i-butyl.

[0025] Some compounds (for example from EP-A-596298; WO 95/20572,EP-A-668267; WO 95/26954; WO 96/25395; WO 96/35664; WO 97/02243; WO97/01535; WO 97/36868; WO 98/05638) require substituted cyclicaminocarboxylic esters of the general formula (IV) as precursors.

[0026] For certain of these compounds disclosed, for example, inEP-A-596298; WO 95/20572; EP-A-668267; WO 95/26954; WO 96/25395; WO96/35664; WO 97/02243; WO 97/01535; WO 97/36868; WO 98/05638, apreparation with the use of substituted cyclic aminocarboxylic esters ofthe general formula (IV) in which the cis isomer (IV-a) is the only orat least the predominant isomer may be advantageous.

[0027] Solvents used for the Bucherer-Bergs reaction are, in general,approximately 50% strength aqueous methanol (J. Org. Chem. 53 (1988)4069-4074) or approximately 50% strength aqueous ethanol (J. Chem. Soc.1961, 4372-4379; Chem. Pharm. Bull. 21 (1973) 685-691; Chem. Pharm.Bull. 21 (1973) 2460-2465; Can. J. Chem. 53 (1975) 3339-3350; Can. J.Chem. 57 (1979) 1456-1461). In optimized Bucherer-Bergs reactions, too,the solvent used was aqueous ethanol (J. Heterocycl. Chem. 21 (1984)1527-1531). A further solvent known for the Bucherer-Bergs reaction isN,N-dimethylformamide (Helv. Chim. Acta 67 (1984) 1291-1297). However,if these solvents are used for preparing the hydantoins of the generalformula (III), unsatisfactory yields are obtained. Moreover, theisolated products are contaminated considerably by inorganic fractions.Additional purification operations result in products havingcompositions which vary considerably with respect to cis and transisomers, so that a constant product quality cannot be ensured.

[0028] It has been found that compounds of the formula (III)

[0029] in which

[0030] R¹ is as defined above,

[0031] are obtained by reacting compounds of the formula (II)

[0032] in which

[0033] R¹ is as defined above

[0034] with ammonium carbonate and alkali metal cyanides ortrimethylsilyl cyanide (TMSCN) in the solvent water.

[0035] Surprisingly, by the process according to the invention, thecompounds of the formula (III) can be obtained in high yield and purityand with a high and reproducible proportion of the cis isomer (III-a)

[0036] in which

[0037] R¹ represents OR³,

[0038] where

[0039] R³ represents alkyl.

[0040] In the general formulae (II), (III) and (III-a), the radical

[0041] R¹ represents OR³,

[0042] where

[0043] R³ preferably represents C₁-C₄-alkyl.

[0044] Particularly preferably, R³ represents methyl, ethyl, n-propyl,n-butyl or i-butyl.

[0045] Very particularly preferably, R³ represents methyl.

[0046] Emphasis is given to the compound of the formula (III-a), inwhich R³ represents methyl.

[0047] The compounds of the formula (III) and the isomers of theformulae (III-a) and (III-b) are novel and form part of thesubject-matter of this invention.

[0048] In the general formula (II-b), the variable R¹ is as definedabove.

[0049] Compounds of the formula (III) can be hydrolysed by known methodsto give the compounds of the formula (I)

[0050] in which

[0051] R¹ is as defined above

[0052] and then esterified by known methods to compounds of the formula(IV).

[0053] Preferred alkali metal cyanides which can be used for preparingthe compounds of the formula (III) are lithium cyanide, sodium cyanideand potassium cyanide; particular preference is given to sodium cyanideand potassium cyanide.

[0054] Based on the ketone, the amount of alkali metal cyanide or TMSCNis from 0.9 to 3 mol per mole of ketone. Preference is given to usingamounts from 1 to 2.5 mol per mole of ketone; particular preference isgiven to amounts from 1.1 to 2 mol of alkali metal cyanide per mole ofketone.

[0055] The amount of ammonium carbonate is from 0.5 to 7 mol of ammoniumcarbonate per mole of ketone. Preference is given to using amounts from0.8 to 5 mol per mole of ketone; particular preference is given toamounts from 1 to 5 mol of ammonium carbonate per mole of ketone.

[0056] The reaction temperature for the process according to theinvention is from 20 to 100° C.; preference is given to a temperaturerange from 30 to 70° C.

[0057] It is also possible to carry out the reaction under elevated orreduced pressure.

[0058] The reaction product is isolated in a simple manner by filteringthe reaction mixture and drying the filter residue. The filtration iscarried out at a temperature of from 0 to 40° C., preferably at atemperature of from 15 to 30° C.

[0059] In this manner, the desired hydantoins of the formula (III) areobtained in high yield and purity, with a reproducible isomer ratio.

[0060] The process according to the invention can be illustrated, forexample, by the scheme below:

[0061] This invention also provides a process for preparing thecompounds of the formula (III-a)

[0062] in which

[0063] R¹ is as defined above,

[0064] characterized in that compounds of the formula (II),

[0065] in which

[0066] R¹ is as defined above

[0067] are reacted with an alkali metal cyanide and ammonium carbonatein water.

[0068] Particular preference is given to a process for preparing thecompound of the formula (III-a), in which

[0069] R¹ represents OR³,

[0070] where

[0071] R³ represents methyl,

[0072] characterized in that 4-methoxycyclohexanone is reacted with analkali metal cyanide and ammonium carbonate in water.

[0073] Suitable for use as alkali metal cyanides are lithium cyanide,sodium cyanide or potassium cyanide; preference is given to sodiumcyanide and potassium cyanide. Particular preference is given to sodiumcyanide.

[0074] Based on the compound of the formula (II), the amount of alkalimetal cyanide is from 0.9 to 3 mol per mole of the compound of theformula (II). Preference is given to amounts of from 0.9 to 2.5 mol permole of the compound of the formula (II); particular preference is givento amounts of from 1 to 2 mol of alkali metal cyanide per mole of thecompound of the formula (II).

[0075] At the same time, the amount of ammonium carbonate is from 0.8 to2 mol of ammonium carbonate per mole of the compound of the formula(II). Preference is given to using amounts of from 1 to 1.8 mol per moleof the compound of the formula (II).

[0076] The amount of the solvent water is from 500 to 3000 ml of waterper mole of the compound of the formula (II); preference is given to anamount of water of from 1000 to 2500 ml per mole of the compound of theformula (II).

[0077] The reaction temperature for the process according to theinvention is from 20 to 100° C.; preference is given to a temperaturerange of from 30 to 70° C.

[0078] The reaction product is isolated in a simple manner by filteringthe reaction mixture and drying the filter residue. The filtration iscarried out at a temperature of from 0 to 40° C., preferably at atemperature of from 0 to 20° C.

[0079] This invention also provides a process for isolating the compoundof the formula (III-a),

[0080] in which

[0081] R¹ is as defined above,

[0082] characterized in that compounds of the formula (III) (cis/transmixtures (III-a)/(III-b)) are treated with aqueous ammonia, and thesolid which remains undissolved is isolated in a known manner.

[0083] Based on the trans isomer of the formula (III-b) present in themixture, the amount of ammonia is from 1 to 30 mol per mole of the transisomer of the formula (III-b). Preference is given to amounts of from 4to 20 mol per mole of the trans isomer of the formula (III-b);particular preference is given to amounts of from 6 to 15 mol of ammoniaper mole of the trans isomer of the formula (III-b).

[0084] The amount of the solvent water is from 500 to 3000 ml of waterper mole of the compound of the formula (III); preference is given to anamount of water of from 1000 to 2500 ml per mole of the compound of theformula (III).

[0085] The temperature for the process according to the invention isfrom 0 to 100° C.; preference is given to a temperature range of from 10to 60° C.

[0086] The hydantoins of the general formula (III) can be hydrolysed byknown methods to the amino acids of the general formula (I), which canthen be esterified by known methods to give compounds of the formula(IV).

[0087] The present invention also provides substituted cyclicaminocarboxylic acids of the general formula (I)

[0088] in which

[0089] R¹ represents OR³,

[0090] where

[0091] R³ represents alkyl, preferably C₁-C₄-alkyl.

[0092] The substituted cyclic aminocarboxylic acids of the generalformula (I) can be present either as mixtures of the cis isomers (I-a)and trans isomers (I-b), or as pure isomers.

[0093] The compounds of the formula (I) are novel and form part of thesubject-matter of this invention.

[0094] Particular preference is given to compounds of the generalformula (I) in which

[0095] R¹ represents OR³,

[0096] where

[0097] R³ represents methyl or ethyl.

[0098] Very particular preference is given to compounds of the generalformula (I-a), in which

[0099] R¹ represents OR³,

[0100] where

[0101] R³ represents methyl or ethyl.

[0102] Substituted cyclic aminocarboxylic acids of the formula (I) oraminocarboxylic esters of the formula (IV) are intermediates in thepreparation of other compounds which are used, for example, as activecompounds in plant protection or as pharmaceutically active compounds.

[0103] Thus, for example, EP-A-596 298, WO 95/20572, EP-A-668 267, WO95/26954, WO 96/25395, WO 96/35664, WO 97/02243, WO 97/01535, WO97/36868, WO 98/05638 disclose that substituted cyclic aminocarboxylicacids are required for preparing substituted phenylketoenols which canbe used as pesticides and herbicides.

[0104] The subject-matter of the invention is illustrated by theexamples below, without limiting it in any way.

PREPARATION EXAMPLES Comparative Example 1

[0105]

[0106] 26.9 g [280 mmol] of ammonium carbonate and 5.88 g [120 mmol] ofsodium cyanide are initially charged in 110 ml of water. Starting atroom temperature, a solution of 7.7 g [60 mmol] of4-methoxy-cyclohexanone in 110 ml of ethanol is added dropwise. Thereaction mixture is stirred at 55-60° C. for 16 hours and thenconcentrated completely (according to HPLC, the cis/trans ratio is66:34). The crude product is stirred with 100 ml of 50% strength aqueousethanol for 1 hour, cooled to 0-5° C., stirred at 0-5° C. for 1 hour andfiltered. The filter residue is dried, giving 12.07 g of a solid havinga product content of 57.8% (HPLC, compared to standard), resulting in ayield of 58.7% of theory; the cis/trans ratio is 91:9. Elementalanalysis shows a sodium content of 16%.

Comparative Example 2

[0107] The procedure of Comparative Example 1 was repeated. Followingwork-up, a product having a cis/trans ratio of 80:20 was obtained.

Example 1

[0108]

[0109] 134.6 g [1.4 mol] of ammonium carbonate and 29.4 g [0.6 mol] ofsodium cyanide are initially charged in 560 ml of water. Starting atroom temperature, 38.5 g [0.3 mol] of 4-methoxy-cyclohexanone are addeddropwise. The reaction mixture is stirred at 55-60° C. for 16 hours,cooled to 0-5° C. and stirred at this temperature for 2 hours. The solidis filtered off with suction and dried. This gives 57.88 g of a solidhaving a product content of 93.4% (HPLC, compared to standard),resulting in a yield of 90.9% of theory; the cis/trans ratio is 71:29.Elemental analysis shows a sodium content of 1.2%.

Example 2

[0110] 134.6 g [1.4 mol] of ammonium carbonate and 22.05 g [0.45 mol] ofsodium cyanide are initially charged in 560 ml of water. Starting atroom temperature, 38.5 g [0.3 mol] of 4-methoxy-cyclohexanone are addeddropwise. The reaction mixture is stirred at 55-60° C. for 4 hours,cooled to 0-5° C. and stirred at this temperature for 2 hours. The solidis filtered off with suction and dried. This gives 57.64 g of a solidhaving a product content of 93.7% (HPLC, compared to standard),resulting in a yield of 90.8% of theory; the cis/trans ratio is 72:28.Elemental analysis shows a sodium content of 1.3%.

Example 3

[0111] 134.6 g [1.4 mol] of ammonium carbonate and 16.17 g [0.33 mol] ofsodium cyanide are initially charged in 560 ml of water. Starting atroom temperature, 38.5 g [0.3 mol] of 4-methoxy-cyclohexanone are addeddropwise. The reaction mixture is stirred at 55-60° C. for 4 hours,cooled to 0-5° C. and stirred at this temperature for 2 hours. The solidis filtered off with suction and dried. This gives 61.02 g of a solidhaving a product content of 94.1% (HPLC, compared to standard),resulting in a yield of 96.5% of theory; the cis/trans ratio is 71:29.

Example 4

[0112] The procedure of Example 3 is repeated. This gives 59.54 g of asolid having a product content of 93.6% (HPLC, compared to standard),resulting in a yield of 93.7% of theory; the cis/trans ratio is 71:29.

Example 5

[0113] 134.6 g [1.4 mol] of ammonium carbonate and 16.17 g [0.33 mol] ofsodium cyanide are initially charged in 560 ml of water. Starting atroom temperature, 38.5 g [0.3 mol] of 4-methoxy-cyclohexanone are addeddropwise. The reaction mixture is stirred at 55-60° C. for 4 hours andthen stirred at room temperature overnight. At room temperature thesolid is filtered off with suction and dried. This gives 58.5 g of asolid having a product content of 95.4% (HPLC, compared to standard),resulting in a yield of 93.9% of theory; the cis/trans ratio is 71:29.

Example 6

[0114]

[0115] 43.2 g [0.45 mol] of ammonium carbonate and 29.4 g [0.6 mol] ofsodium cyanide are initially charged in 560 ml of water. Starting atroom temperature, 38.5 g [0.3 mol] of 4-methoxy-cyclohexanone are addeddropwise. The reaction mixture is stirred at 55-60° C. for 4 hours,cooled to 0-5° C. and stirred at this temperature for 2 hours. The solidis filtered off with suction and dried. This gives 26.4 g of a solid,resulting in a yield of 44.4% of theory; the cis/trans ratio is>99.7:0.3.

[0116] Melting point: 267-268° C. (sublimation).

[0117]¹H-NMR (400 MHz, d-DMSO): δ=1.38-1.48 (m; 2H), 1.57-1.68 (m; 4H),1.91-1.95 (m; 2H), 3.14-3.17 (m; 1H), 3.23 (s; 3H), 8.37 (s; 1H) ppm.

Example 7

[0118] 34.6 g [0.36 mol] of ammonium carbonate and 29.4 g [0.6 mol] ofsodium cyanide are initially charged in 560 ml of water. Starting atroom temperature, 38.5 g [0.3 mol] of 4-methoxy-cyclohexanone are addeddropwise. The reaction mixture is stirred at 55-60° C. for 4 hours,cooled to 0-5° C. and stirred at this temperature for 2 hours. The solidis filtered off with suction and dried. This gives 18.8 g of a solid,resulting in a yield of 31.6% of theory; the cis/trans ratio is99.4:0.6.

Example 8

[0119] 28.8 g [0.3 mol] of ammonium carbonate and 16.2 g [0.33 mol] ofsodium cyanide are initially charged in 560 ml of water. Starting atroom temperature, 38.5 g [0.3 mol] of 4-methoxy-cyclohexanone are addeddropwise. The reaction mixture is stirred at 55-60° C. for 4 hours,cooled to 0-5° C. and stirred at this temperature for 2 hours. The solidis filtered off with suction and dried. This gives 15.5 g of a solid,resulting in a yield of 26.1% of theory; the cis/trans ratio is99.2:0.8.

Example 9

[0120]

[0121] 13.5 g [140 mmol] of ammonium carbonate and 1.62 g [33 mmol] ofsodium cyanide are initially charged in 56 ml of water. Starting at roomtemperature, 4.3 g [30 mmol] of 4-ethoxy-cyclohexanone are addeddropwise. The reaction mixture is stirred at 55-60° C. for 4 hours,cooled to 0-5° C. and stirred at this temperature for 2 hours. The solidis filtered off with suction and dried. This gives 5.55 g of a solid(78.8% of theory); the cis/trans ratio is 72:28.

[0122]¹H-NMR (400 MHz, d-DMSO): δ=1.09 (t; 3H, cis), 1.12 (t; 3H,trans), 1.3-1.48 (m; 2H, cis+trans), 1.57-1.64 (m; 4H, cis+trans),1.77-1.95 (m; 2H, cis+trans), 3.25-3.3 (m; 1H, cis+trans), 3.40 (q; 2H,trans), 3.45 (q; 2H, cis), 8.40 (s, br; 1H, cis+trans) ppm.

[0123] Further examples of the formula (III)

[0124] which may be mentioned are:

Example 10

[0125] R¹=O—^(n)C₃H₇ m.p.>250° C. cis/trans=87/13

Example 11

[0126] R¹=O—^(n)C₄H₉ m.p.>250° C. cis/trans=85/15

Example 12

[0127] R¹=O—^(i)C₄H₉ m.p.>250° C. cis/trans=51/49

Example 13

[0128]

[0129] In an autoclave, 19.8 g [0.1 mol] of4-methoxycyclohexane-1-spiro-5′-hydantoin (cis/trans ratio 71:29), 4 g[0.1 mol] of sodium hydroxide and 400 ml of water are heated at 160° C.for 24 hours. With ice-cooling, the reaction mixture is adjusted to pH 3using hydrochloric acid and concentrated substantially under reducedpressure. The remaining water is removed by azeotropic distillation withtoluene. This gives 29.6 g of a solid.

[0130] According to GC/MS (after silylation), 3.7% of starting materialand 89.3% of 4-methoxycyclohexane-1-amino-carboxylic acid are present;the cis/trans ratio is 70:30.

[0131] GC/MS(sil.): m/e=302 (product (disilylated)—15), 200 (base peak,product (disilylated)—CO₂SiMe₃), 168 (200—MeOH).

Example 14

[0132]

[0133] In an autoclave, 7.9 g [40 mmol] ofcis-4-methoxycyclohexane-1-spiro-5′-hydantoin, 160 ml of water and 1.6 g[40 mmol] of sodium hydroxide are heated at 160° C. for 24 hours. Withice-cooling, the reaction mixture is adjusted to pH 3 using hydrochloricacid and substantially concentrated under reduced pressure. Theremaining water is removed by azeotropic distillation with toluene. Thisgives 11.2 g of a solid.

[0134] m.p.>400° C.

[0135]¹H-NMR (400 MHz, d₆-DMSO): δ=3.17 (m, 1H, CHOCH₃), 3.22 (s, 3H,OCH₃) ppm.

Example 15

[0136]

[0137] In an autoclave, 1 g [5 mmol] oftrans-4-methoxycyclohexane-1-spiro-5′-hydantoin, 20 ml of water and 0.2g [5 mmol] of sodium hydroxide are heated at 160° C. for 24 hours. Withice-cooling, the reaction mixture is adjusted to pH 3 using hydrochloricacid and substantially concentrated under reduced pressure. Theremaining water is removed by azeotropic distillation with toluene.

[0138] This gives 0.8 g of a solid.

Example 16

[0139]

[0140] 6.9 g [40 mmol] of cis-4-methoxycyclohexane-1-aminocarboxylicacid are suspended in 50 ml of anhydrous methanol. The mixture isbriefly heated to reflux and then cooled to 0° C. At 0-5° C., 6.9 g [58mmol] of thionyl chloride are added dropwise. The mixture is stirred at0-5° C. for half an hour, then allowed to warm to room temperature,heated to 40° C. and stirred at 40° C. overnight. The reaction mixtureis filtered, the filter residue is washed with 20 ml of methanol and thefiltrate is concentrated. The residue is stirred with 50 ml of methyltert-butyl ether and filtered off with suction, and the residue isdried. This gives 5.6 g of methylcis-4-methoxy-cyclohexane-1-aminocarboxylate hydrochloride (63% oftheory).

[0141] m.p. 298° C.

[0142]¹H-NMR (400 MHz, d-DMSO): δ=1.64-1.80 (m; 4H), 1.88-1.96 (m; 4H),3.23 (s; 3H), 3.29-3.32 (m; 1H), 3.76 (s; 3H), 8.67 (s, br; 3H) ppm.

Example 17

[0143]

[0144] In the same manner as described in Example 12, methyltrans-4-methoxycyclohexane-1-aminocarboxylate hydrochloride is prepared.

[0145] m.p. 173° C.

[0146]¹H-NMR (400 MHz, d₆-DMSO): δ=185-2.37 (4 m, 8H, CH₂), 3.32 (s, 3H,CHOCH₃), 3.50 (“d”, 1H, CHOCH₃), 3.82 (s, 3H, OCH₃), 8.94 (br, 3H,^(⊕)NH₃) ppm.

[0147] Similarly to Example 15, the following amino acid esters of theformula (IV) are obtained

Example 18

[0148] R¹=O—C₂H₅ R²=Me m.p.>220° C.

Example 19

[0149] R¹=O—^(n)C₃H₇ R²=Me m.p.>220° C.

Example 20

[0150] R¹=O—^(n)C₄H₉ R²=Me m.p. 183° C.

Example 21

[0151] R¹=O—^(i)C₄H₉ R²=Me m.p. 179° C.

Example 22

[0152] R¹=OMe R²=Et MS(silyl.): m/e=273 (M⁺)

Example 23

[0153] R¹=OMe R²=^(n)Bu ¹H-NMR

[0154]¹H-NMR (400 MHz, d-DMSO): δ=0.88-0.92 (t; 3 H), 1.32-1.41 (m; 2H), 1.57-1.68 (m; 2 H), 1.69-2.1 (m; 10 H), 3.23 (s; 3 H), 3.27-3.31 (m;1H), 4.14-4.18 (m; 2 H), 8.77 (s, br; 3 H) ppm.

Example 24

[0155]

[0156] 10.2 g of the compound of the formula (III) where R¹=OR³, R³being methyl (8-methoxy-1,3-diazaspiro[4.5]decane-2,4-dione; 97% pure,cis/trans ratio=75:25) are stirred at 55° C. in 86 ml of water and 9.8 gof 26% strength ammonia for 4 hours. The mixture is cooled to 0-5° C.and stirred at this temperature for 2 hours. The solid is filtered offwith suction and dried. This gives 5.37 g of a solid; the cis/transratio is 98.3:1.7.

Example 25

[0157] Example 24 is repeated, except that the mixture is stirred atroom temperature for 4 hours. This gives 5.03 g of a solid having acis/trans ratio of 97.7:2.3.

Example 26

[0158] 10.2 g of the compound of the formula (III) where R¹=OR³, R³being methyl (8-methoxy-1,3-diazaspiro[4.5]decane-2,4-dione; 97% pure,cis/trans ratio=75:25) are stirred at 55° C. in 86 ml of water and 6.5 gof 26% strength ammonia for 4 hours. The mixture is cooled to 0-5° C.and stirred at this temperature for 2 hours. The solid is filtered offwith suction and dried. This gives 5.73 g of a solid; the cis/transratio is 97.3:2.7.

Example 27

[0159] 10.4 g of the compound of the formula (III) where R¹=OR³, R³being methyl (8-methoxy-1,3-diazaspiro[4.5]decane-2,4-dione; 95.3% pure,cis/trans ratio=98.2:1.8) are stirred at 55° C. in 17 ml of water and0.69 g of 26% strength ammonia for 4 hours. The mixture is cooled to0-5° C. and stirred at this temperature for 2 hours. The solid isfiltered off with suction and dried. This gives 9.58 g of a solid; thecis/trans ratio is >99.7:0.3.

1. Compounds of the formulae (IV-a) and (IV-b)

in which R¹ represents OR³, R² represents alkyl and R³ represents alkyl.2. Compounds of the formulae (IV-a) and (IV-b) according to claim 1, inwhich R¹ represents OR³, R² represents C₁-C₆-alkyl and R³ representsC₁-C₄-alkyl.
 3. Compounds of the formulae (IV-a) and (IV-b) according toclaim 1, in which R¹ represents OR³, R² represents methyl, ethyl,n-propyl or n-butyl and R³ represents methyl, ethyl, n-propyl, n-butylor i-butyl.
 4. Compounds of the formula (III)

in which R¹ is as defined above.
 5. Compounds of the formula (III-a)

in which R¹ is as defined above.
 6. Compounds of the formula (II-b)

in which R¹ is as defined above.
 7. Process for preparing compounds ofthe formula (III),

in which R¹ is as defined above, characterized in that compounds of theformula (II)

in which R¹ is as defined above are reacted with ammonium carbonate andalkali metal cyanides or trimethylsilyl cyanide (TMSCN) in the solventwater.
 8. Process for preparing compounds of the formula (III-a),

in which R¹ is as defined above, characterized in that compounds of theformula (II)

in which R¹ is as defined above are reacted with an alkali metal cyanideand ammonium carbonate in water.
 9. Process for isolating compounds ofthe formula (III-a)

in which R¹ is as defined above, characterized in that compounds of theformula (III) are treated with aqueous ammonia.
 10. Compounds of thegeneral formula (I)

in which R¹ represents OR³, where R³ represents alkyl.
 11. Compounds ofthe formula (I) according to claim 9, in which R¹ represents OR³, whereR³ represents C₁-C₄-alkyl.
 12. Compounds of the formula (I) according toclaim 9, in which R¹ represents OR³, where R³ represents methyl orethyl.